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• Chapter 7

Lymphatic System
and Immunity

• ©2 0 2 0 M c G ra w -H ilE d u c a tio n .A lrig h ts re s e rv e d .A u th o riz e d o n ly fo rin s tru c to ru s e in th e c N la


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u .c tio n o rfu rth e rd is trib u tio n p e rm ite d w ith o u th e p rio rw rite n c o n s e n to fM c G ra w -H ilE d u c a tio n .
The Lymphatic and Immune
Systems
Points to ponder
•What are the parts of the lymphatic system and what
are their functions?
•What are the first and second lines of defense in
nonspecific immunity?
•What is cell-mediated and antibody-mediated immunity
in the third line of defense?
•What are the different types of B cells in these
processes?
•What is active and passive immunity? Be able to
describe how they are different and examples of each.
•Understand allergic reactions, tissue rejection, and
immune system disorders as problems that the immune
system faces.
4 functions of the lymphatic system
• Lymphatic capillaries absorb excess tissue fluid
and return it to the bloodstream

• Lymphatic capillaries (lacteals) in the small


intestine absorb fats associated with proteins

• Works in the production, maintenance and


distribution of lymphocytes in the body

• Helps in defense against pathogens


What are the components of the
lymphatic system?
Copyright © The McGraw-Hill Companies, Inc. Permission required for
reproduction or display.

Tonsil: patches of lymphatic tissue;


help to prevent entrance of
Right lymphatic duct: pathogens by way of the nose
empties lymph into the and mouth
right subclavian vein Red bone marrow: site for the
origin of all types of blood cells
Axillary lymph nodes:
located in the underarm region Thymus: lymphatic tissue where
T lymphocytes mature and
learn to tell "self" from "nonself"
Thoracic duct: empties Spleen: cleanses the blood of
lymph into the left cellular debris and bacteria, while
subclavian vein resident lymphocytes respond to
the presence of antigens
tissue
fluid
lymphatic
capillary

Inguinal lymph nodes: tissue cell


located in the groin region; blood
cleanse lymph and alert capillary
the immune system to
pathogens
Lymphatic vessels
• One-way valve system that carries fluid called
lymph

• Made of capillaries, vessels and ducts

• Function to return tissue fluid (includes water,


solutes and cell products) to the bloodstream

• The larger vessels are similar in structure to


veins and even have valves
Classifying lymphatic organs
• Primary
– Red bone marrow.
– Thymus gland,.

• Secondary
– Lymph nodes,
– Spleen, Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

lobule
cortex capsule

310 µm 641 µm 641 µm 381 µm


lymphocyte monocyte cortex medulla capsule medulla white pulp red pulp

Red bone marrow Thymus gland Lymph node Spleen


(thymus, spleen): © Ed Reschke/Peter Arnold; (marrow): © R. Valentine/Visuals Unlimited; (lymph): © Fred E. Hossler/Visuals Unlimited
Primary lymphatic organs
• Red bone marrow
– Site of blood cell production
– More bones in children have red marrow and it decreases as we
age. [ sternum, vertebrae, ribs, pelvic region, upper end of femur &
humerus]
– Some white blood cells ( B Lymphocytes) mature here

• Thymus gland
– Bilobed gland found in the thoracic cavity superior to the heart
– Largest in children and shrinks as we age
– Produce hormone= thymosin, aid in maturation of T lymphocytes
– Immature T lymphocytes move from the marrow to the thymus
where they mature and 95% will stay
Secondary lymphatic organs
• Lymph nodes, filter lymph
– Small, oval-shaped structures found along the
lymphatic vessels filled B cells, T cells and
macrophages
– Common in the neck, armpit and groin regions

• Spleen, filters blood from worn out RBC


– In the upper left region of the abdominal cavity
– Filled with white pulp containing lymphocytes, & red
pulp is involved with filtering the blood from worn out
RBC
Innate Immune Defenses
Immunity—killing or removing foreign
substances, pathogens, and cancer cells from
the body.
There are two branches of our immune system:
innate and adaptive.
• Innate—fully functional without previous exposure
to a pathogen.
• Adaptive—is initiated when exposed to a pathogen.
What do the nonspecific defenses
include?
• First line of defense:
– Barriers to entry: physical and chemical

• Second line of defense:


– Phagocytic white blood cells
– Inflammatory response
– Protective proteins: complement and
interferons
The first line of defense
Innate Defense
• Physical barriers
– Skin
– Tears, saliva and urine physically flush out microbes
– Mucous membranes line the respiratory, digestive, reproductive and
urinary tracts.
– Resident bacteria/normal flora that inhabit the body use available
nutrients and space thus preventing pathogens from taking up
residence

• Chemical barriers
– Secretions of the oil glands
– Lysozyme found in saliva, tears and sweat
– Acidic pH of the stomach and vagina.
Overview of Innate Immune Defenses
The second line of defense:
Phagocytic white blood cells
• Includes neutrophils and macrophages

• Both leave circulation and move into tissue

• Cells that are important in the inflammatory


response
Inflammatory response
• Four hallmark symptoms are redness, heat, swelling and pain

• Histamine is released by mast cells causes the capillaries to dilate


and become more permeable including the phagocytic white blood
cells

• Increased blood flow to an area causes the skin to redden &


increases the warmth that inhibits some pathogens.

• Increased blood flow also brings more white blood cells to an injured
area with neutrophils being the first scouts to kill pathogens & form
pus.

• This response can be short-lived but if the neutrophils cannot control


the damage, cytokines (chemicals) will call in more white blood cells
including monocytes that live longer & become macrophages
Steps of the inflammatory response

Skin
2. Macrophages phagocytize pathogens
and release cytokines, which stimulate
Tissue the inflammatory response.
neutrophil
monocyte
mast cell
macrophage
histamine
injured tissue
1. Injured tissue cells and mast cells pathogen
release histamine, which causes
capillaries to dilate and increases cytokines
blood flow.

blood clot

Capillary 4. Blood clotting walls off 3. Neutrophils and monocytes (become


capillary and prevents macrophages) squeeze through the
blood loss. capillary wall and phagocytize pathogens.
The second line of defense:
Protective proteins
• Complement : complement
– Group of blood plasma proteins. proteins

- Complement the immune response.


– Amplify the inflammatory response by
binding to mast cells to release membrane
histamine attack complex

– Some form a membrane attack


complex that make holes in some
bacteria and viruses that causes them
to burst

• Interferons: fluids

– Proteins produced by virally infected


cells sent out to warn neighboring
healthy cells
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What are the innate immune
defenses?
Innate defenses

Barriers Protective Phagocytes and Inflammatory


to entry proteins natural killer cells response

skin and
mucous
membranes
dendritic
cell

pathogens
antimicrobial
molecules macrophage cytokines

neutrophil
monocyte natural
killer ells

complement proteins
and interferons
in plasma

Figure 7.3 Overview of innate immune defenses.


Adaptive Immune Defenses
• Come into play when innate (nonspecific) defenses
have failed to prevent an infection.
• Provide some protection against cancer.
• Respond to antigens (immune system recognizes as
foreign).
• Fragments of bacteria, viruses, molds, and parasitic
worms can all be antigenic.
How Adaptive Defenses Work 2

There are two pathways of adaptive immunity:


cell-mediated and antibody-mediated.
• In antibody-mediated immunity (also called humoral
immunity), B cells produce antibodies that bind to
free antigens in body fluids.
• In cell-mediated immunity, T cells kill cells that are
presenting a specific “foreign” antigen.
What do the specific defenses include?
Acquired Defenses
• Third line of defense:
– Helps protect us against specific pathogens
when nonspecific defenses fail
– Helps protect us against cancer.
– Respond to a foreign body (antigen).
– Depends on the action of B and T cells.
(lymphocytes).
– Clonal Selection Model.
What are the types of B cells?

• B cells produce plasma cells and memory


cells.
– Plasma cells produce specific antibodies.
– Memory cells are ready to produce
antibodies in the future.
What are the types of T cells?

• T cells regulate immune response;


produce various types of T cells.
– Cytotoxic T (Tc) cells kill virus-infected and
cancer cells.
– Helper T (TH) cells regulate immunity.
– Memory T (Tc and TH) cells are ready to kill
in the future.
Summary of the types of B and T cells
Characteristics of B cells
Antibody-mediated immunity by B cells=
Humoral Immunity
• Each B cell has a unique receptor called a BCR (B cell receptor)
that binds to a specific antigen

• This binding and cytokines secreted by helper T cells result in clonal


expansion in which this B cell makes copies of itself

• Most of the cells produced are plasma cells that secrete antibodies

• Other cells become memory cells which result in long-term immunity

• After an infection has passed plasma cells undergo apoptosis


(programmed cell death) leaving memory cells
Antibody-mediated immunity by B cells
Humeral Immunity B cell
B–cell
receptor
antigens
(BCR)

Activation cytokines from T cells Helper T cells secrete


cytokines that stimulate
cells to clone
Clonal expansion

Cloned B cells become


plasma cells ( IgD)

Memory B cells

Plasma cells are large & have Plasma cells

extensive ER to produce
antibodies
Apoptosis
antigen
Apoptosis
Antibody-mediated immunity by B cells
antigen cytokines
from T cells
B cell B-cell
receptor
antigens
(BCR)

Plasma cells
Memory B cells

a. Activation: When a B cell receptor binds to an antigen


activation occurs. b. Clonal expansion – During clonal expansion, cytokines secreted by
helper T cells stimulate B cells to clone mostly into plasma cells or memory cells.

Apoptosis

Figure 7.7 B cell clonal selection.


c. Apoptosis – Apoptosis, or programmed cell death, occurs to plasma cells
left in the system after the infection has passed.
Structure of antibodies
• A Y-shaped protein.
antigen-binding
antigen
• Neutralization—antibodies coat V
sites antigen binds
to binding site
V
viruses and toxins completely, & V V
removing the threat. shape of antigen fits
C
C
light
chain
shape of binding site
C C
• The trunk of the Y is a constant heavy
chain
region that determines the class
of the antibody a.
C = constant
V = variable

• The end of the arms (Y) are the


variable regions where specific
antigens bind.
• Y can be monomer, dimer or
pentamers

b.
What are the 5 classes of
antibodies?
Characteristics of T cells
Third line of defense: Cell-mediated
immunity by T cells
• Each T cell has a unique receptor called a TCR ( T cell receptor) that
will bind to an antigen, but it needs the help of an antigen-presenting
cell (APC)= macrophage.

• Macrophage engulfs an antigen (bacteria), breaks it down and a piece


of it is displayed on a groove of an MHC protein (= human leukocyte
antigens, HLA). then presents it to T cells in the lymph node or spleen

• The T cell will specifically recognize the combination of the MHC


protein and the piece of antigen

• Clonal expansion will occur leading to mostly helper T cells, cytotoxic T


cells and a few memory T cells

• After an infection has passed, helper and cytotoxic T cells undergo


apoptosis leaving memory cells
Cell-mediated immunity by T cells
T–cell receptor (TCR)

T cell

Activation

self
bacterium
Macrophage acts as
antigen
(MHC I)
cytokines

antigen-presenting cell (APC


Which will present it at
lymph node or spleen
Clonal expansion Macrophage

Two classes of MHC:


MHC I , activate Cytotoxic T cells Cytotoxic

MHC II, activate Helper T cells


T cell

Apoptosis

Memory
T cell
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Helper and cytotoxic T cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.

• Helper T cells:
cytotoxic T cell
– Secrete cytokines that help many
immune cells function
target cell
(virus-infected
• Cytotoxic T cells: or cancer cell)

– Have 2 types of vacuoles :


1- Granzymes. Cytotoxic T cell
vesicle granzyme
2- Perforins. perforin

– Perforins punch holes in target


cells (cancer or virus-infected
cells) followed by granzymes that Perforin
cause the cell to undergo forms hole
in target cell. Granzymes
apoptosis enter through the
hole and cause
target cell to
Target cell undergo apoptosis.
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Overview of Adaptive Immune Defenses

Access the text alternative for these images


What are the types of B and T cells?
memory
B cell

B cell

antibody
Antibody- plasma
mediated BCR cell
immunity
APC antigen
TCR
memory
TH cell

Adaptive
defenses
TH cell activated
TH cell

activated
Cell-
TC cell
mediated
immunity
antigen

memory
TC cell

virus-infected
cell
TCcell TCR

Figure 7.6 Overview of adaptive immune defenses .


Immunity
• Is the ability to combat diseases and
cancer

• Can be brought about naturally through an


infection or artificially through medical
intervention

• There are two types of immunity: active


and passive
Active immunity
• The individual’s body makes antibodies against a
particular antigen

• This can happen through natural infection or through


immunization involving vaccines

• Primary exposure is shorter-lived and slower to respond


while a secondary exposure is a rapid, strong response

• This type of immunity is usually long-lasting

• It depends on memory B and T cells


Examples of immunizations: a type of
active immunity

Suggested Immunization Schedule


Vaccine Age (months) Age (years)

Hepatitis B Birth–18 11–12


Diphtheria, tetanus,2, 4, 6, 15–18 4–6
pertussis (DTP)
Tetanus and 11–12
pertussis only
Haemophilus 2, 4, 6, 12–15
influenzae, type b
Polio 2, 4, 6–18 4–6, 11–12
Pneumococcal 2, 4, 6, 12–15
Measles, mumps, 12–15 4–6, 11–12
rubella (MMR)
Varicella 12–18 11–12
(chicken pox)
Meningococcal 11–12
Hepatitis A 12–23 11–12
(in selected areas) 2–18

a.

high primary response secondary response

second exposure
Plasma Antibody
Concentration

to vaccine

first exposure
to vaccine

low
0 30 60 90 120 150 180
Time (days)
b.
a: © Michael Newman/PhotoEdit
How Immunizations Cause Active
Immunity
Passive immunity

• An individual is given
prepared antibodies
against a particular
antigen

• This type of immunity is


short-lived a. Antibodies (IgG) cross the placenta. b. Antibodies (IgG, IgA) are
secreted into breast milk.

• This can happen naturally


as antibodies are passed
from mother to fetus (IgG
IgA) or artificially via an
injection of antibodies

c. Antibodies can be injected by a


physician.
How can the immune system react that
maybe harmful to the body?
• Allergies
• Tissue rejection
• Immune system disorders
Allergies
• Hypersensitivities to harmless substances such as pollen,
food or animal hair= Allergens.

• An immediate allergic response is caused by the IgE


antibodies that are attached to mast cells in tissues &
basophiles in blood.

• When allergens attach to these IgE molecules histamine is


released and we see allergy symptoms.

• An immediate allergic response that occurs when the allergen


enters the bloodstream is anaphylactic shock in which the
blood pressure drops and is life-threatening

• Delayed allergic responses are initiated by memory T cells


such as seen with poison ivy
Tissue rejection
• This can occur when cytotoxic T cells respond to
tissue that is not recognized as “self” tissue

• This can be controlled by giving patients


immunosuppressive drugs and by transplanting
organs that have the same MHC proteins in the
donor and recipient

• Currently we are trying to grow organs in the lab


that can be transplanted with less rejection
Disorders of the immune system
• Autoimmune diseases:
– A disease in which cytotoxic T cells or antibodies attack
the body’s own cells as if they were foreign
– Examples: multiple sclerosis, and rheumatoid arthritis

• Acquired Immunodeficiency disease syndrome


AIDS/ HIV
– HIV is a virus that attacks the immune system by
destroying T helper cells. Virus makes more copies of
itself.
– AIDS is the set of symptoms caused by HIV virus

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